The evolving role of inflammation in obesity and the metabolic syndrome

Lee, Yong-Ho; Pratley, Richard E.

doi:10.1007/s11892-005-0071-7

Cited by 326 publications

(240 citation statements)

References 57 publications

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“…Although there is convincing evidence that obesity creates an inflammatory state (44) and that weight loss decreases circulating CRP levels in adults (45,46), controversy surrounds the role of exercise that may occur independently of weight loss; it is postulated that the relative contributions from "fitness" versus "fatness" on inflammatory markers may depend on gender, age, and disease status (47). In this group of disease-free postmenopausal women, the effect of our intervention on CRP levels seemed to have been The TER was calculated from a general linear model for each biomarker, estimating a parameter with anti-logarithm corresponding to the ratio of adjusted geometric means for the exercise intervention group over the control group; this ratio was assumed to be common at 6 months and 12 months postrandomization.…”

Section: Discussionmentioning

confidence: 99%

“…Among the proposed mechanisms relating CRP changes to exercise (46)(47)(48), loss of body fat predominates and, for women in the ALPHA Trial, seems the most plausible. The infiltration of inflammatory cells into adipose tissue ultimately increases circulating CRP levels (46) by producing TNF-a and IL-6 (18,44). Conversely with fat loss, circulating levels of TNF-a and IL-6 might be expected to decrease.…”

Section: Discussionmentioning

confidence: 99%

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Inflammatory Marker Changes in a Yearlong Randomized Exercise Intervention Trial among Postmenopausal Women

Friedenreich

Neilson

Woolcott

et al. 2012

Cancer Prevention Research

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Chronic low-grade inflammation is a possible risk factor for cancer that may be modifiable with long-term exercise. Very few randomized controlled trials (RCT) have studied the isolated effects of exercise on lowgrade inflammation exclusively in postmenopausal women. The Alberta Physical Activity and Breast Cancer Prevention Trial, a 2-armed RCT in healthy postmenopausal women, examined how 1 year of moderate to vigorous aerobic exercise, compared with usual inactivity, influenced circulating inflammatory markers. Baseline, 6-month, and 12-month serum was analyzed by direct chemiluminescent immunoassays to measure high sensitivity C-reactive protein (CRP) and ELISAs to measure interleukin 6 (IL-6) and TNF-a. Intention to treat analyses were conducted with linear mixed models. Statistically significant differences in CRP were observed over 12 months for exercisers versus controls (treatment effect ratio ¼ 0.87, 95% CI ¼ 0.79-0.96, P ¼ 0.005), but not in IL-6 or TNF-a. A statistically significant trend (P trend ¼ 0.021) of decreasing CRP with increasing exercise adherence and stronger intervention effects on CRP in women with higher baseline physical fitness (P heterogeneity ¼ 0.040) was found. The intervention effect on CRP became statistically nonsignificant with adjustment for dietary fiber intake change and seemed to be mediated by fat loss. Low-grade inflammation may be lowered with exercise, but confounding by dietary intake occurred and should be considered in future studies. Further trials are needed to corroborate our findings about the optimal dose of exercise required to lower CRP levels and effect modification of CRP changes by levels of body fatness and fitness. Cancer Prev Res; 5(1); 98-108. Ó2011 AACR.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Inflammatory Marker Changes in a Yearlong Randomized Exercise Intervention Trial among Postmenopausal Women

Friedenreich

Neilson

Woolcott

et al. 2012

Cancer Prevention Research

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“…1 Obesity, and in particular abdominal obesity, is commonly accompanied by elements of the metabolic syndrome, including insulin resistance, hypertension and dyslipidemia and is associated with impaired immune function and an increased risk of chronic inflammatory diseases, such as type 2 diabetes, atherosclerosis, certain cancers and respiratory disorders. 2,3 It therefore poses a major challenge to public health care. Obvious contributing factors to the rise in obesity are a reduction in levels of physical activity coupled with a rise in consumption of processed, energy-dense food.…”

Section: Introductionmentioning

confidence: 99%

“…Obesity is associated with a state of chronic systemic low-grade inflammation, and obese humans have elevated circulating levels of a variety of inflammatory markers, including the cytokines leptin, interleukin-1 receptor antagonist (IL-1Ra) and interleukin-6 (IL-6). 3 Leptin is significantly elevated (approximately fourfold) in obese people and correlates with percentage body fat. 21 The effect is also striking for IL-1Ra; serum IL-1Ra levels are sevenfold higher in morbidly obese patients, where they are positively correlated with BMI.…”

Section: Introductionmentioning

confidence: 99%

Stress-induced cytokine responses and central adiposity in young women

et al. 2007

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Background: Evidence suggests that people who are more responsive to psychological stress are at an increased risk of developing obesity. However, the biological mechanisms underlying this phenomenon are poorly understood. The cytokines leptin, interleukin-1 receptor antagonist (IL-1Ra) and interleukin-6 (IL-6) play a key role in fat metabolism and abnormal circulating levels of these proteins have been reported in obese people and in individuals subject to stress. Objective: This study investigated whether cytokine responses to acute mental stress are associated with adiposity in healthy young women. Design and Subjects: A laboratory study of 67 women, aged 18-25 years, recruited from University College London. Measurements: Height, weight and waist circumference were measured and body fat mass was estimated by bioelectrical impedance body composition analysis. Laboratory mental stress testing was carried out and blood pressure and heart rate were recorded at baseline, during two moderately challenging tasks (Stroop and speech) and during recovery 40-45 min post-stress. Blood samples taken at baseline, immediately post-stress and 45 min post-stress, were used for assessment of circulating cytokines. Saliva samples taken throughout the session were assessed for cortisol. Results: Women who had larger cytokine responses to stress were more abdominally obese than women with smaller cytokine stress responses. Specifically, there was a positive correlation between waist circumference and stress-induced increases in plasma levels of leptin (r ¼ 0.35, Po0.05) and IL-1Ra responses (r ¼ 0.29, Po0.05). There was also a significant positive correlation between prolonged diastolic blood pressure responses to stress and measures of total and abdominal obesity (r ¼ 0.28-0.33, Po0.05). Conclusion: Increased cytokine production could be a mechanism linking stress and abdominal obesity.

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“…Circulating TNF-α is increased in obesity [14] and has been implicated as a causative factor in obesity-associated insulin resistance and the pathogenesis of type 2 diabetes [15,16]. In this study, we used the cultured murine pancreatic beta cell line MIN6 and pancreatic islets, as well as human amylin promoter luciferase reporter constructs, to examine the effect of TNF-α on amylin expression and further explore the mechanisms involved.…”

Section: Introductionmentioning

confidence: 99%

TNF-α acutely upregulates amylin expression in murine pancreatic beta cells

Cai

Wang

et al. 2010

Diabetologia

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Aims/hypothesis Amylin, a secretory protein mainly produced by pancreatic beta cells, is elevated in the circulation of patients with diseases related to acute and chronic inflammation, including acute pancreatitis, pancreas graft rejection, obesity and insulin resistance. TNF-α is involved in these disorders. We investigated the effect of TNF-α on amylin levels and the underlying mechanisms, using murine pancreatic beta cell line MIN6 and pancreatic islets. Methods Amylin, proinsulin and prohormone convertase 1/3, 2 (Pc1/3, Pc2 [also known as Pcsk1/3 and Pcsk2, respectively]) mRNA levels, and amylin promoter and nuclear factor κB (NF-κB) activation were examined by real-time PCR and luciferase reporter assay, respectively. Amylin protein level and mitogen-activated protein kinase phosphorylation were detected by western blot. Activator protein 1 (AP1) activation was examined by electrophoretic mobility shift assay (EMSA).Results TNF-α acutely induced amylin expression at the transcriptional level and increased proamylin and the intermediate form of amylin in MIN6 cells and islets. However, it had no effect on proinsulin, Pc1/3 and Pc2 expression. Studies with (1) MIN6 cells treated with inhibitors of MEK1/2, c-Jun-N-terminal kinase (JNK) or protein kinase CK PKC ð z Þ, (2) MIN6 cells expressing a c-Jun-dominant negative construct and (3) islets from Fos knockout mice demonstrated that TNF-α induced amylin expression through the PKC z Àextracellular signal-regulated kinase (ERK)/JNK pathways. EMSA showed that PKC z , JNK and ERK1/2 were involved in TNF-α-induced AP1 activation, suggesting that TNF-α induces murine amylin expression through the PKC z ÀERK1=2ÀAP1 and PKC z À JNKÀAP1 pathways. Further studies showed that TNF-α also induced murine amylin expression through the phosphatidylinositol 3 kinase-NF-κB signalling pathway and enhanced human amylin promoter activation through NF-κB and AP1. Conclusions/interpretation TNF-α acutely induces amylin gene expression in beta cells through multiple signalling pathways, possibly contributing to amylin elevation in acute inflammation-related pancreatic disorders.

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The evolving role of inflammation in obesity and the metabolic syndrome

Cited by 326 publications

References 57 publications

Inflammatory Marker Changes in a Yearlong Randomized Exercise Intervention Trial among Postmenopausal Women

Inflammatory Marker Changes in a Yearlong Randomized Exercise Intervention Trial among Postmenopausal Women

Stress-induced cytokine responses and central adiposity in young women

TNF-α acutely upregulates amylin expression in murine pancreatic beta cells

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